cRGD-ZW700-1c Imaging Conjugate for Stable Integrin Targeting
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Solution Overview
Problem
Existing near-infrared (NIR) fluorophores used for imaging have poor stability in vivo, leading to rapid metabolism and low signal-to-background ratios due to non-specific uptake and undesirable fluorescence in non-target tissues.
Innovation Solution
Conjugating a ZW700-1c dye with a cRGD peptide through a carbon-carbon bond to create a charge-balanced imaging agent that enhances stability and reduces non-specific binding, improving biodistribution and clearance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If known fluorophores are used for NIR imaging, then imaging capability is achieved, but stability is poor leading to rapid metabolism and low signal-to-background ratio
Solution Approach 1:
The patent combines ZW700-1c fluorophore with cRGD peptide through a carbon-carbon bond to create a composite imaging agent. This composite structure integrates the optical properties of the fluorophore with the targeting capabilities of the peptide, achieving both high stability and improved signal-to-background ratio through selective cellular uptake
Solution Approach 2:
The patent modifies the chemical structure by replacing a key bond with a carbon-carbon bond conjugation, changing the bond strength parameter to achieve vastly increased stability. Additionally, the charge-balancing properties are optimized to improve biodistribution and reduce non-specific binding
2Manufacturing precision
If advanced fluorophores are used to lower non-specific uptake, then signal-to-background ratio improves, but stability decreases becoming labile in blood
Solution Approach 1:
The patent changes the bond type to carbon-carbon conjugation which provides vastly increased stability in blood compared to other fluorophores, while maintaining the charge-balancing properties that achieve signal-to-background ratio of at least 1.1
3Productivity
If fluorophores are designed for rapid clearance, then biodistribution improves, but signal intensity may be reduced due to faster elimination
Solution Approach 1:
The charge-balancing properties of the conjugate are optimized to achieve efficient renal clearance while the cRGD peptide component increases circulation time by facilitating specific cellular uptake, creating a balanced pharmacokinetic profile
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The conjugate achieves a signal-to-background ratio of at least 1.1, providing higher resolution imaging by maintaining optical signal integrity and efficient renal clearance.
Implementation Method 1
Near infrared (NIR) fluorescence has potential importance in the medical field, particularly in diagnostics and image-guided surgery
Implementation Method 2
irradiating the tissue or cells at a wavelength absorbed by the conjugate
Data Source
AI summary
The present invention relates to an imaging agent comprising a ZW700-1c dye conjugated to a cyclic-RGD peptide targeting ligand. The conjugate of the invention has superior stability and desirable in vivo properties as compared to other zwitterionic near-infrared contrast agents. The invention also relates to a method of imaging cells of a subject using the imaging agent. In particular, the invention relates to a method of imaging or identifying cells of a subject which are or are suspected of overexpressing one or more integrins using the imaging agent. Such cells include tumors, inflammatory cells, and cells undergoing angiogenesis.